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Based on transcriptomic analysis of tumor tissues, differentially expressed genes in the combination therapy group were related to biological processes concerning angiogenesis, such as regulation of blood vessel diameter, regulation of tube diameter, and regulation of tube size. Our data suggest that XWH enhances the anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway. Combination therapy with anlotinib and XHW may be a novel therapeutic strategy for lung cancer patients.Dog bladder cancer (BC) is mostly muscle-invasive (MI) with poor prognosis, and its pathogenesis is close to human MIBC. Three-dimensional (3D) organoid culture ensures novel knowledge on cancer diseases including BC. Recently, we have established dog BC organoids (BCO) using their urine samples. BCO recapitulated the epithelial structures, characteristics, and drug sensitivity of BC-diseased dogs. However, organoids from dog normal bladder epithelium are not established yet. Therefore, the present study aimed to establish dog normal bladder organoids (NBO) for further understanding the pathogenesis of dog BC and human MIBC. The established NBO underwent various analyzes including cell marker expressions, histopathological structures, cancer-related gene expression patterns, and drug sensitivity. NBO could be produced non-invasively with a continuous culturing and recapitulated the structures and characteristics of the dog's normal bladder mucosal tissues. Different drug sensitivities were observed in each NBO. The analysis of RNA sequencing revealed that several novel genes were changed in NBO compared with BCO. NBO showed a higher expression of p53 and E-cadherin, but a lower expression of MDM2 and Twist1 compared with BCO. These results suggest that NBO could be a promising experimental 3D model for studying the developmental mechanisms of dog BC and human MIBC.The role of H2S in urothelial carcinoma (UC) is still unclear. Here we have evaluated the expression of H2S producing enzymes as well as the effect of endogenous and exogenous H2S on human bladder UC cells. In human UC cells the expression of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST); is significantly lower as compared to healthy cells. A modulatory role for the H2S pathway is supported by the finding that, the overexpression of CSE or CBS, but not 3-MST, inhibits cell proliferation and promotes apoptosis. A similar effect is obtained by using exogenous H2S. Diallyl trisulfide (DATS), which is a fully characterized H2S donor, inhibits the proliferation of UC cells in a time and concentration-dependent manner as well as promotes apoptosis. Moreover, DATS also induces autophagy, as determined by transcriptomic and western blot analysis. Finally, DATS inhibits mRNA expression levels of canonical markers of epithelial-mesenchymal transition by limiting migration and clonogenic ability of human UC cells in vitro. In conclusion, in urothelial carcinoma, there is an impairment of H2S pathway that involves CSE and CBS- derived hydrogen sulfide. Thus, targeting H2S signaling pathway in urothelial carcinoma could represent a novel therapeutic strategy.Excessive osteoclast differentiation and activation are closely associated with the development and progression of osteoporosis. Natural plant-derived compounds that can inhibit osteoclastogenesis are an efficient strategy for the prevention and treatment of osteoporosis. Tereticornate A (TA) is a natural terpene ester compound extracted from the leaves and branches of Eucalyptus gracilis, with antiviral, antibacterial, and anti-inflammatory activities. However, the effect of TA on osteoclastogenesis and the underlying molecular mechanism remain unclear. Based on the key role of the NF-κB pathway in the regulation of osteoclastogenesis and the observation that TA exhibits an anti-inflammatory effect by inhibiting NF-κB activity, we speculated that TA could exert anti-osteoclastogenesis activity. Herein, TA could inhibit the RANKL-induced osteoclast differentiation and formation of F-actin rings in RAW 264.7 cells. Mechanistically, TA downregulated the expression of c-Src and TRAF6, and also suppressed the RANKL-stimulated canonical RANK signaling pathways, including AKT, MAPK (p38, JNK, and ERK), and NF-κB; ultimately, downregulating the expression of NFATc1 and c-Fos, the key transcriptional factors required for the expression of genes (e.g., TRAP, cathepsin K, β-Integrin, MMP-9, ATP6V0D2, and DC-STAMP) that govern osteoclastogenesis. Our findings demonstrated that TA could effectively inhibit RANKL-induced osteoclastogenesis via the downregulation of c-Src and TRAF6 and the inhibition of RANK signaling pathways. Thus, TA could serve as a novel osteoclastogenesis inhibitor and might have beneficial effects on bone health.Scholars suggest that improving hazard perception (HP) skills among different road users can lead to safer driving. To this end, a small number of countries have developed a national hazard perception test for their licensing procedures. The purpose of the current research is to develop and validate a new video-based hazard prediction test for the Lithuanian driving context. Eighty-eight drivers participated in the study. Initially, 25 naturalistic clips were included and edited into a hazard prediction test following the "what happens next?" paradigm. The overall score of the test was higher for experienced drivers when compared with novices. On further inspection the overall group difference was driven by 12 clips. The Lithuanian Hazard Perception test HPT-LIT featuring static images (Tūskė et al., 2019) and Hazard Perception Questionnaire developed by White et al. (2011) were used to validate the new test. This new version of the test (12 clips, LHP12) showed acceptable psychometric properties. Drivers with less driving experience demonstrated poorer hazard prediction skills than experienced drivers. The results revealed a negative correlation between hazard prediction scores on LHP12 and crash involvement in the novice driver group, as well as a positive correlation between prediction scores and self-reported hazard prediction skills. It was concluded that the new Lithuanian hazard test shows potential for future research.<br /><br /> Diabetes is a major public health challenge, affecting millions of people worldwide. Abnormal physiology in diabetes, particularly hypoglycemia, can cause driver impairments that affect safe driving. While diabetes driver safety has been previously researched, few studies link real-time physiologic changes in drivers with diabetes to objective real-world driver safety, particularly at high-risk areas like intersections. To address this, we investigated the role of acute physiologic changes in drivers with type 1 diabetes mellitus (T1DM) on safe stopping at stop intersections.<br /><br /> 18 T1DM drivers (21-52years, μ=31.2years) and 14 controls (21-55years, μ=33.4years) participated in a 4-week naturalistic driving study. At induction, each participant's personal vehicle was instrumented with a camera and sensor system to collect driving data (e.g., GPS, video, speed). Video was processed with computer vision algorithms detecting traffic elements (e.g., traffic signals, stop signs). Stop intersections were geolocatedl physiologic fluctuations in drivers with diabetes to driver safety based on unsafe stopping at stop-controlled intersections, providing recommendations for clinicians aimed at improving patient safety, fair licensing guidelines, and targets for developing advanced driver assistance systems.<br /><br />This study links acute, abnormal physiologic fluctuations in drivers with diabetes to driver safety based on unsafe stopping at stop-controlled intersections, providing recommendations for clinicians aimed at improving patient safety, fair licensing guidelines, and targets for developing advanced driver assistance systems.<br /><br /> As the population ages, it is important to consider whether older adults tend to have healthier lives. This study examined temporal trends in cognitive function among community-dwelling Japanese older adults.<br /><br /> The data source for this study was Integrated Longitudinal Studies on Aging in Japan (ILSA-J). We collected representative values for the Mini-Mental State Examination (MMSE) score obtained in 2010 and 2017; mean, standard deviation, and prevalence of ≤23 as cognitive impairment and ≥28 as intact cognitive function. Six cohorts (n=8,575) in 2010 and seven cohorts (n=6,089) in 2017 were included (age range 65-89). One-group meta-analyses were conducted to calculate pooled means of MMSE scores, the pooled prevalence of MMSE scores ≤23 and ≥28, and 95% confidence intervals (CIs).<br /><br /> The mean MMSE score was higher in 2017 than in 2010 for all age groups in both men and women. The prevalence of MMSE ≤23 was lower in 2017 than in 2010 for all age groups for men and was lower in 2017 than in 2010 for all age groups other than for women aged 75-79 years. The prevalence of MMSE ≥28 was higher in 2017 than in 2010 for all age groups in both men and women. In addition, the pooled means of years of education was lower in 2010 than in 2017, which might be an explanatory factor.<br /><br /> This study suggests that the cognitive function of community-dwelling Japanese older adults has improved in recent years. Future studies need to identify factors associated with the improvement.<br /><br />This study suggests that the cognitive function of community-dwelling Japanese older adults has improved in recent years. Future studies need to identify factors associated with the improvement.The soft lattice of lead-halide perovskite nanocrystals (NCs) allows tuning their optoelectronic characteristics via anion exchange by introducing halide salts to a solution of perovskite NCs. Similarly, cross-anion exchange can occur upon mixing NCs of different perovskite halides. This process, though, is detrimental for applications requiring perovskite NCs with different halides in close proximity. We study the effects of various stabilizing surface ligands on the kinetics of the cross-anion exchange reaction, comparing zwitterionic and ionic ligands. The kinetic analysis, inspired by the "cage effect" for solution reactions, showcases a mechanism where the surface capping ligands act as anion carriers that diffuse to the NC surface, forming an encounter pair enclosed by the surrounding ligands that initiates the anion exchange process. The zwitterionic ligands considerably slow down the cross-anion exchange process, and while they do not fully inhibit it, they confer improved stability alongside enhanced solubility relevant for various applications.Step-scheme heterojunctions formed between two firmly bound photocatalysts facilitate charge separation due to interfacial charge transfer, which is usually illustrated by the gain or loss of electrons in the constituent photocatalysts characterized by in situ irradiated X-ray photoelectron spectroscopy. This technique provides a steady-state view of charge distribution but overlooks the transient and complex dynamics of charge transfer, trapping, and recombination. To provide a molecular-level and dynamic view of these processes, we investigated the behaviors of photogenerated charge carriers within an inorganic/organic TiO2/polydopamine S-scheme heterojunction using ultrafast transient absorption spectroscopy and time-resolved photoluminescence spectroscopy. We found the interfacial charge transfer within the step-scheme heterojunction occurred at a smaller shorter time scale than recombination, leading to efficient charge separation. Moreover, the charge-discharge property of polydopamine induces electron backflow, which should be avoided in practical photocatalytic applications.